Influenza vaccination strategies for 2020-21 in the context of COVID-19

Background Influenza vaccination prevents people from influenza-related diseases and thereby mitigates the burden on national health systems when COVID-19 circulates and public health measures controlling respiratory viral infections are relaxed. However, it is challenging to maintain influenza vaccine services as the COVID-19 pandemic has the potential to disrupt vaccination programmes in many countries during the 2020/21 winter. We summarise available recommendations and strategies on influenza vaccination, specifically the changes in the context of the COVID-19 pandemic. Methods We searched websites and databases of national and international public health agencies (focusing on Europe, North and South America, Australia, New Zealand, and South Africa). We also contacted key influenza immunization focal points and experts in respective countries and organizations including WHO and ECDC. Results Available global and regional guidance emphasises the control of COVID-19 infection in immunisation settings by implementing multiple measures, such as physical distancing, hand hygiene practice, appropriate use of personal protective equipment by health care workers and establishing separate vaccination sessions for medically vulnerable people. The guidance also emphasises using alternative models or settings (eg, outdoor areas and pharmacies) for vaccine delivery, communication strategies and developing registry and catch-up programmes to achieve high coverage. Several novel national strategies have been adopted, such as combining influenza vaccination with other medical visits and setting up outdoor and drive through vaccination clinics. Several Southern Hemisphere countries have increased influenza vaccine coverage substantially for the 2020 influenza season. Most of the countries included in our review have planned a universal or near universal influenza vaccination for health care workers, or have made influenza vaccination for health care workers mandatory. Australia has requested that all workers and visitors in long term care facilities receive influenza vaccine. The UK has planned to expand the influenza programme to provide free influenza vaccine for the first time to all adults 50-64 years of age, people on the shielded patient list and their household members and children in the first year of secondary school. South Africa has additionally prioritised people with hypertension for influenza vaccination. Conclusions This review of influenza vaccination guidance and strategies should support strategy development on influenza vaccination in the context of COVID-19.


NETWORK OF COVID-19 EVIDENCE REVIEWS
Influenza virus causes epidemics each year which usually occur in winter and spring in temperate regions and throughout the year (with more than one peak) in tropical regions [1,2]. Influenza virus can cause mild to severe disease in the human population and accounts for about 291 000-646 000 respiratory deaths annually, placing a substantial burden on health care systems globally [3]. Influenza activity in the past few months was lower than expected in many countries due to the implementation of lockdown and physical distancing measures which were adopted to minimise the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease   [4][5][6][7]. However, it is expected that influenza activity will increase in the upcoming (2020-21) season as these measures are being lifted, and there are concerns that national health systems could be overwhelmed by the co-circulation of COVID-19 and influenza viruses [8]. Additionally, influenza virus is the most frequent secondary pathogen identified in patients with COVID-19, due to paucity of data and conflicting results in published literature regarding the outcome of such co-infections, the clinical significance of such co-infections remains unclear [9][10][11][12][13]. For example, a large case-control study in England, UK found that influenza virus co-infection was associated with increased COVID-19 severity and higher risk of mortality, while another case-control study among hospitalised COVID-19 patients in Wuhan, China reported an opposite impact of influenza co-infection [11,13]. Whilst a COVID-19 vaccine does not yet exist, influenza vaccination, although does not provide 100% protection, protects many people, especially medically vulnerable people, from influenza-related severe morbidity and mortality and thereby reduces the burden on national health systems in the upcoming influenza season [14]. However, influenza vaccination services can be difficult to sustain in the presence of COVID-19 [15,16]. In this review, we provide a summary of regional and national recommendations and strategies on influenza vaccination, specifically the changes in the context of COVID-19.

METHODS
We conducted a rapid review on regional and national influenza vaccination strategies and generic guidance on immunization in the context of the COVID-19 pandemic. We searched websites and databases of national and international public health agencies (focusing on Europe, North and South America, Australia, New Zealand, and South Africa) for relevant documents and press releases. We also contacted key influenza immunization focal points and experts in respective countries and organizations including World Health Organisation (WHO), the WHO Regional Office for Americas (PAHO) and European Centre for Disease Prevention and Control (ECDC). Table 1 provides a summary of results by region and country. Globally, there is generic guidance on immunization during the COVID-19 pandemic published by WHO, although not specific to influenza. WHO recommends that immunisation should be prioritised and continued during the COVID-19 pandemic and, where suspended, countries should reinstate immunisation services as soon as possible [15]. They recommend that countries should suspend mass vaccination campaigns temporarily and focus on the provision of vaccines from fixed site immunisation services, using additional and / or alternative locations to increase vaccine coverage. They also recommend that countries develop effective communication strategies and catch-up vaccination programmes to achieve a high vaccine coverage. On the basis of this guiding principle, PAHO specifically recommends that influenza vaccination should be prioritized whilst the capacity of the health system is intact and the provision of essential health services continues [19]. To limit the spread of COVID-19 in immunisation settings, PAHO specifically recommends conducting vaccination sessions in well-ventilated areas with frequent environmental disinfection, scheduling vaccination appointments to avoid crowding, implementing hand hygiene practice and appropriate use of personal protective equipment by health care workers. To protect medically vulnerable people, PAHO recommends establishing separate vaccination sessions exclusively for older people and people with pre-existing medical conditions. It is recommended that people with confirmed or suspected COVID-19 outside health care facilities postpone vaccination until symptoms resolve following negative test results of COVID-19 or 14 days later if testing is not feasible. People with COVID-19 in health care facilities should be vaccinated upon recovery and prior to discharge. Staff must not attend vaccination if they are unwell. European Commission includes influenza vaccination as one of the key strategies for "EU health preparedness for COVID-19 outbreaks" this winter (van der Hoek W 2020, personal communication, 4 September). VIEWPOINTS RESEARCH THEME 7: UNCOVER -USHER INSTITUTE NETWORK OF COVID-19 EVIDENCE REVIEWS Fever after vaccination should not be assumed to be due to receipt of an influenza vaccine and should be clinically assessed and tested for COVID-19.

New
Zealand [34][35][36] No change in the target groups, but influenza vaccination is prioritised to certain groups (details in next column).
Plan to increase coverage in sev-  According to a recent government press release, influenza immunisation programme will be expanded and more investment will be made. Some specific measures are considered to improve vaccination, such as using a proactive call and recall system to encourage influenza vaccination and continuing the school age influenza vaccination programme to invite all eligible children if possible.
No specific recommendations but some challenges in the coming season are anticipated. For example, vaccinees may be concerned about maintaining social distancing when being given the vaccine.
Norway [40,41] 1. All personnel in health services with regular patient contacts should be offered free vaccine in the workplace. 2. An adjuvant influenza vaccine will be used to target residents older than 65 y in long-term care settings (eg, nursing homes) and people on the waiting list to these institutions and those older than 80 y receiving home care.
More influenza vaccines have been ordered (0.4 million more doses than last year).

NETWORK OF COVID-19 EVIDENCE REVIEWS
We identified recommendations for the ongoing or upcoming influenza season in 13 countries, including five countries in the WHO regions of America, five in Europe, two in the Western Pacific region and one in the African region. These countries have adopted several novel immunisation strategies in addition to those in the regional and global recommendations ( Table 1). For example, Canada, Germany and the Netherlands recommend combining influenza vaccination with other vaccines and / medical visits for each individual in one visit to reduce contacts [25,42,45]. Greece (and WHO regional office of America) allows only one carer to accompany the vaccine [44]. Canada, Greece and South Africa recommend vaccinees and carers use face masks appropriately [25,44,46]. Moreover, while Australia has set up outdoor and drive-through vaccination clinics, the Netherlands have recommended outdoor vaccination clinics but decided against drive-through clinics [27,45]. Canada will decide after looking at experience from Australia [25].
In addition to nonspecific recommendations on immunisation, some countries have made greater efforts to expand influenza vaccination programmes this year. For example, several Southern Hemisphere countries (eg, Australia, Chile and New Zealand) have increased their vaccination coverage substantially [20,28,34]. Norway, the Netherlands and UK have also planned to increase influenza vaccine coverage by making more investment to national influenza programmes and developing vaccination registry systems and catch-up programmes although the availability of substantially higher number doses of vaccine (compared to previous years) is a limiting factor [37,40,45]. With regard to priority groups, special attention has been paid to vaccinating health care workers and people in long term care facilities. For example, most of the countries included in our review have planned universal or nearly universal influenza vaccination for health care workers, or have made influenza vaccination for health care workers mandatory [26,35,38,40,46]. Australia has also requested all people entering long term care facilities to be vaccinated against influenza [29,30]. WHO (and the Regional office for the Western Pacific) also recommend that all residents and staff in long term care facilities be vaccinated against seasonal influenza [17,47]. Moreover, UK has recommended expanding the priority group list and additionally providing free influenza vaccine to all adults 50-64 years of age, people who are on the shielded patient list and members of their household and children in the first year of secondary school [37]. South Africa has additionally prioritised people with hypertension in 2020 [46].

DISCUSSION
Several new strategies have been recommended or adopted at global, regional, and national levels to promote influenza vaccine uptake and control the spread of COVID-19 in immunisation settings.
Several countries included in this review have increased their investment in national influenza vaccination programmes or have planned to increase their investment to achieve a higher uptake in the upcoming influenza season. Influenza virus activity has been low in the past few months in the Southern Hemisphere due to the implementation of multiple stringent measures to decrease SARS CoV-2 transmission (eg, physical distancing, closure of schools, non-essential businesses, workplaces and other indoor settings), but the situation may be different for the Northern Hemisphere in the upcoming winter as it is unlikely to keep all the measures in place throughout the whole winter and the adherence with restrictions in the general population may decrease over time [1]. As the measures are gradually lifted, some settings (eg, schools and childcare) reopen and social activities increase, the transmission of influenza virus is expected to rise [48]. In such circumstances, a high influenza vaccine coverage is expected to be beneficial in the upcoming influenza season whist COVID-19 co-circulates and an effective COVID-19 vaccine does not yet exist [18,49,50]. This, however, can be challenging to achieve in many countries for several reasons. First, according to a recent survey, vaccination programmes in nearly 60 countries have been disrupted by the COVID-19 pandemic, making it difficult to maintain the provision of influenza vaccination services [16]. Second, due to the fear of COVID-19, people may be unwilling to leave home for vaccination [16]. To achieve a high influenza vaccine uptake, good communication strategies, vaccination record systems and catch-up campaigns are needed to promote the use of influenza vaccination services in the general population and identify missed vaccinations [15]. During the COVID-19 pandemic, there have been increasing concerns regarding vaccine hesitancy due to misinformation and public concerns about vaccine safety and its potential side effects [51,52]. Countries should build vaccine confidence by addressing public concerns regularly, enhancing community engagement, building public trust with health authorities, and helping health care workers build high-quality interactions with the community to address concerns [53]. On the other hand, the COVID-19 pandemic may have changed VIEWPOINTS RESEARCH THEME 7: UNCOVER -USHER INSTITUTE NETWORK OF COVID-19 EVIDENCE REVIEWS government and public perception about the importance of respiratory vaccines, leading to an increased demand for seasonal influenza vaccination for the upcoming season. Consistent with this, a recent study using Google trends data found a peak in worldwide interest in influenza and pneumococcal vaccines coinciding with the COVID-19 pandemic [54]. A sudden and large increase in demand may outpace the production capacity of seasonal influenza vaccines, which has not been augmented significantly in the most recent years [55]. It is of concern whether the manufacturing capacity is sufficient to match an increased demand for influenza vaccine at the global level. The availability of influenza vaccine is likely to be, as in the past, very limited in many countries, especially in low-and lower middle-income countries, given the uneven distribution of influenza vaccines across countries. According to a recent survey, the WHO African, Southeast Asia and Eastern Mediterranean regions altogether accounted for only 5% of the total number of influenza vaccine doses distributed globally in 2017 [56]. Additionally, countries may face challenges related to the need for increased vaccine storage and delivery capacity following an increase in the stock of influenza vaccine [19].
Prioritising influenza vaccination to the most vulnerable people can optimise the impact on population health. Healthcare workers are at increased risk of exposure to influenza virus [57,58]. Older adults, especially those in aged care settings, and people with medical conditions are at increased risk of developing severe disease and dying from influenza or COVID-19 infection [59][60][61] Vaccinating these groups is crucial in the upcoming season as it protects health care workers and prevents severe influenza infections, easing pressure on health care systems that have been already stressed by the COVID-19 pandemic [62][63][64]. Recent reviews have shown that influenza vaccination is safe, and not associated with increased risk of serious adverse events (eg, Guillain-Barré syndrome, respiratory function, cardiac arrest, and acute myocardial infarction), although may lead to a slightly increased risk of fever and local reactions such as tenderness, swelling and redness at the injection site [65][66][67][68]. There are no available data to suggest that the minor adverse effects of influenza vaccine lead to an increased risk of COVID-19 infections or severe outcomes. On the contrary, several studies found that people who were vaccinated against influenza were less likely to have severe COVID-19 compared to unvaccinated people [69].
Despite the substantial benefits of influenza vaccination, the delivery of influenza vaccination (and other vaccination) services can pose a challenge to the safety of vaccinators and the community in the context of COVID-19 because contacts between vaccinators, vaccinees and carers during vaccination visits may increase the risk of COVID-19 transmission. All the guidance identified in this review emphasizes the necessity to implement enhanced infection control measures in immunisation settings. Very specific measures have been adopted, which can be grouped into the following categories, including physical distancing measures, using alternative delivery models, locations and settings to provide vaccination (eg, outdoor areas, pharmacies and other health services), implementing hand hygiene practice and / using face masks, and ensuring the availability and appropriate use of personal protective equipment among vaccinators. The novel strategies (eg, combining influenza vaccination with other visits and setting up outdoor and drive through vaccination clinics) adopted by countries can help inform decision making in immunisation programmes in other countries. According to a recent modelling study, these measures, if implemented well, could be effective in reducing contacts between individuals and the risk of COVID-19 infection during vaccination visits [70]. However, in practice, implementation of these measures can be challenging and requires cooperative efforts. For example, countries need to develop detailed and specific instructions and provide clear guidance in different aspects and scenarios for vaccine providers and other health care workers at vaccination service delivery sites. Vaccine providers need to communicate with vaccinees and the community to ensure their understanding of and compliance with the infection control measures. Although we identified little information from resource-limited regions, implementing some of the infection control measures is also likely to be feasible and effective in these settings [70]. The availability of vaccine delivery infrastructures (eg, primary care services) and sustainable funding for vaccination programmes will facilitate national influenza vaccination policy formation in resource-limited regions. Strengthened vaccine delivery systems will also benefit the rapid introduction and up-scaling of new vaccines (eg, COVID-19 vaccine) in future [71].
This summary of guidance and strategies on influenza vaccination at global, regional and national level should support strategy development on influenza vaccination in the context of the COVID-19 pandemic.
Authorship contributions: All authors have contributed to the search. XW and DK have extracted data. XW wrote the first draft of the manuscript with input from all authors. All authors have read and approved the final manuscript.

Competing interests:
Harry Campbell is the Co-Editor in Chief of the Journal of Global Health. To ensure that any possible conflict of interest relevant to the journal has been addressed, this article was reviewed according to best practice guidelines of international editorial organisations. HN reports grants and personal fees from SANOFI PAS-TEUR, personal fees from Janssen, Abbvie and Bill And Melinda Gates Foundation, grants from Innovative Medicines Agency and NIHR, grants and personal fees from World Health Organization outside the submitted work. HC reports grants and personal fees from WORLD HEALTH Organization, grants from EU Innovative Medicines Initiative, grants and personal fees from Bill and Melinda Gates Foundation during the conduct of the study. JP reports grants from Foundation for Influenza Epidemiology, grants from World Health Organization and Sanofi Pasteur outside the submitted work. The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no further conflicts.